CA2771775C - Compounds and compositions as protein kinase inhibitors - Google Patents
Compounds and compositions as protein kinase inhibitors Download PDFInfo
- Publication number
- CA2771775C CA2771775C CA2771775A CA2771775A CA2771775C CA 2771775 C CA2771775 C CA 2771775C CA 2771775 A CA2771775 A CA 2771775A CA 2771775 A CA2771775 A CA 2771775A CA 2771775 C CA2771775 C CA 2771775C
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- CA
- Canada
- Prior art keywords
- propan
- pyrazol
- methyl
- pyrimidin
- chloro
- Prior art date
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- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
- LCWPXLBWVNEYIW-LBPRGKRZSA-N methyl n-[(2s)-1-[[4-[1-propan-2-yl-3-[2,4,5-trifluoro-3-(methanesulfonamido)phenyl]pyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C(F)=C(F)C=2)F)=N1 LCWPXLBWVNEYIW-LBPRGKRZSA-N 0.000 claims 1
- SJTRSVMDXLVDFY-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[2,4-difluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C(F)=CC=2)F)=N1 SJTRSVMDXLVDFY-ZDUSSCGKSA-N 0.000 claims 1
- IDDGSCPILQDMST-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[2,5-difluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(F)C=2)F)=N1 IDDGSCPILQDMST-ZDUSSCGKSA-N 0.000 claims 1
- MKCVFAPLFKXTKT-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[2,6-difluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=CC=2F)F)=N1 MKCVFAPLFKXTKT-ZDUSSCGKSA-N 0.000 claims 1
- BEPGTMTXHVYWRS-HNNXBMFYSA-N methyl n-[(2s)-1-[[4-[3-[2,6-difluoro-3-(propylsulfonylamino)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1F BEPGTMTXHVYWRS-HNNXBMFYSA-N 0.000 claims 1
- FIMRNHGGRIJTEX-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[2-chloro-3-(ethylsulfonylamino)-4,5-difluorophenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCS(=O)(=O)NC1=C(F)C(F)=CC(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1Cl FIMRNHGGRIJTEX-ZDUSSCGKSA-N 0.000 claims 1
- ZKZGAMDUVHYNPH-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[2-chloro-5-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(F)C=2)Cl)=N1 ZKZGAMDUVHYNPH-ZDUSSCGKSA-N 0.000 claims 1
- FCSQNBKYSFKSHZ-AWEZNQCLSA-N methyl n-[(2s)-1-[[4-[3-[2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=CC=2)F)=N1 FCSQNBKYSFKSHZ-AWEZNQCLSA-N 0.000 claims 1
- RMHZWQZTKKHYCT-INIZCTEOSA-N methyl n-[(2s)-1-[[4-[3-[2-fluoro-3-(propylsulfonylamino)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCCS(=O)(=O)NC1=CC=CC(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1F RMHZWQZTKKHYCT-INIZCTEOSA-N 0.000 claims 1
- JUTDCRUMEUQOPM-AWEZNQCLSA-N methyl n-[(2s)-1-[[4-[3-[3-(cyclopropylsulfonylamino)-2,5-difluorophenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(=O)(=O)C3CC3)C=C(F)C=2)F)=N1 JUTDCRUMEUQOPM-AWEZNQCLSA-N 0.000 claims 1
- MISNBEQFUJYEAG-AWEZNQCLSA-N methyl n-[(2s)-1-[[4-[3-[3-(ethylsulfonylamino)-2,4-difluorophenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCS(=O)(=O)NC1=C(F)C=CC(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1F MISNBEQFUJYEAG-AWEZNQCLSA-N 0.000 claims 1
- MFQUQRONWUFERA-HNNXBMFYSA-N methyl n-[(2s)-1-[[4-[3-[3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C=C(NS(C)(=O)=O)C=CC=2)=N1 MFQUQRONWUFERA-HNNXBMFYSA-N 0.000 claims 1
- OYJJSQKATCWOOM-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[3-chloro-2-(methanesulfonamido)pyridin-4-yl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)N=CC=2)Cl)=N1 OYJJSQKATCWOOM-ZDUSSCGKSA-N 0.000 claims 1
- AZFXVYSHIJAZOU-AWEZNQCLSA-N methyl n-[(2s)-1-[[4-[3-[3-chloro-5-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C=C(NS(C)(=O)=O)C=C(Cl)C=2)=N1 AZFXVYSHIJAZOU-AWEZNQCLSA-N 0.000 claims 1
- PCDHTILQESNIQQ-INIZCTEOSA-N methyl n-[(2s)-1-[[4-[3-[3-chloro-5-(propylsulfonylamino)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCCS(=O)(=O)NC1=CC(Cl)=CC(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1 PCDHTILQESNIQQ-INIZCTEOSA-N 0.000 claims 1
- BEJNUMRZYPYGDM-ZDUSSCGKSA-N methyl n-[(2s)-1-[[4-[3-[3-fluoro-2-(methanesulfonamido)pyridin-4-yl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)N=CC=2)F)=N1 BEJNUMRZYPYGDM-ZDUSSCGKSA-N 0.000 claims 1
- RPKHXXHDQCZMJE-PVCZSOGJSA-N methyl n-[(2s)-1-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-(oxan-2-yl)pyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C2OCCCC2)C=2C(=C(NS(C)(=O)=O)C=C(Cl)C=2)F)=N1 RPKHXXHDQCZMJE-PVCZSOGJSA-N 0.000 claims 1
- IFUNYGIIWVIYAY-HNNXBMFYSA-N methyl n-[(2s)-1-[[4-[3-[5-chloro-2-fluoro-3-(propylsulfonylamino)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound CCCS(=O)(=O)NC1=CC(Cl)=CC(C=2C(=CN(N=2)C(C)C)C=2N=C(NC[C@H](C)NC(=O)OC)N=CC=2)=C1F IFUNYGIIWVIYAY-HNNXBMFYSA-N 0.000 claims 1
- GVJFWGLLYQAPCL-AWEZNQCLSA-N methyl n-[(2s)-1-[[4-[3-[5-chloro-3-(cyclopropylsulfonylamino)-2-fluorophenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(=O)(=O)C3CC3)C=C(Cl)C=2)F)=N1 GVJFWGLLYQAPCL-AWEZNQCLSA-N 0.000 claims 1
- HKXKEELLDFNXRA-ZDUSSCGKSA-N methyl n-[(2s)-2-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propyl]carbamate Chemical compound COC(=O)NC[C@H](C)NC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(Cl)C=2)F)=N1 HKXKEELLDFNXRA-ZDUSSCGKSA-N 0.000 claims 1
- XRCYSJXOEWSFPE-UHFFFAOYSA-N n-[3-[4-(2-aminopyrimidin-4-yl)-1-propan-2-ylpyrazol-3-yl]-5-chloro-2-fluorophenyl]methanesulfonamide Chemical compound N=1N(C(C)C)C=C(C=2N=C(N)N=CC=2)C=1C1=CC(Cl)=CC(NS(C)(=O)=O)=C1F XRCYSJXOEWSFPE-UHFFFAOYSA-N 0.000 claims 1
- LDNRMMCYKPMHQR-UHFFFAOYSA-N n-[5-chloro-2-fluoro-3-[4-[2-(methylamino)pyrimidin-4-yl]-1-propan-2-ylpyrazol-3-yl]phenyl]methanesulfonamide Chemical compound CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(Cl)C=2)F)=N1 LDNRMMCYKPMHQR-UHFFFAOYSA-N 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Otolaryngology (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23807309P | 2009-08-28 | 2009-08-28 | |
| US61/238,073 | 2009-08-28 | ||
| US31303910P | 2010-03-11 | 2010-03-11 | |
| US61/313,039 | 2010-03-11 | ||
| PCT/US2010/046930 WO2011025927A1 (en) | 2009-08-28 | 2010-08-27 | Compounds and compositions as protein kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2771775A1 CA2771775A1 (en) | 2011-03-03 |
| CA2771775C true CA2771775C (en) | 2015-01-20 |
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ID=42782253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2771775A Active CA2771775C (en) | 2009-08-28 | 2010-08-27 | Compounds and compositions as protein kinase inhibitors |
Country Status (49)
Cited By (1)
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| WO2022036176A1 (en) | 2020-08-13 | 2022-02-17 | Albert Einstein College Of Medicine | N-cyclyl-sulfonamides useful for inhibiting raf |
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| AR077975A1 (es) | 2009-08-28 | 2011-10-05 | Irm Llc | Derivados de pirazol pirimidina y composiciones como inhibidores de cinasa de proteina |
| MX360932B (es) | 2010-02-25 | 2018-11-21 | Dana Farber Cancer Inst Inc | Mutaciones del protooncogen de serina/treonina-proteina cinasa b-raf (braf) que confieren resistencia a los inhibidores del protooncogen de serina/treonina-proteina cinasa b-raf. |
| US8907270B2 (en) | 2010-06-30 | 2014-12-09 | Schlumberger Technology Corporation | Method and apparatus for gain regulation in a gamma detector |
| RU2622015C2 (ru) * | 2011-11-11 | 2017-06-08 | Новартис Аг | Способ лечения пролиферативного заболевания |
| AR088936A1 (es) * | 2011-11-23 | 2014-07-16 | Novartis Ag | Formulaciones farmaceuticas |
| US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022036176A1 (en) | 2020-08-13 | 2022-02-17 | Albert Einstein College Of Medicine | N-cyclyl-sulfonamides useful for inhibiting raf |
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